No abstract

Background: Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. The aim of the present review was to report current knowledge on oxidative stress related to oral mucosal diseases. Materials and Methods: Articles from 2000 to 2018 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: oxidative stress and oral lichen, oral pemphigus, aphthous stomatitis, oral leukoplakia, oral cancer, oral squamous cell carcinoma and oral carcinoma. All articles were independently screened for eligibility by the authors. Results: This narrative review integrates extensive information from all relevant published studies focusing on oxidative stress in oral mucosal diseases. We outline the pathogenetic function of oxidative stress in the most frequent inflammatory, potentially malignant and malignant diseases of the oral mucosa and provide detailed findings from human research. Conclusion: Although variability in findings between individual studies exists, it justifies the conclusion that oxidative stress is a significant process in the oral mucosal diseases pathogenesis.

Excess palmitate results in activation of ceramide biosynthesis, JNK signaling, and apoptosis in human CPCs. GLP1R activation counteracts this lipotoxic damage via inhibition of ceramide generation, and this may represent a cardioprotective mechanism.

Endothelial cells participate in inflammatory events leading to atherogenesis by regulating endothelial cell permeability via the expression of VE-Cadherin and β-catenin and leukocyte recruitment via the expression of E-Selectins and other adhesion molecules. The protein p66Shc acts as a sensor/inducer of oxidative stress and may promote vascular dysfunction. The objective of this study was to investigate the role of p66Shc in tumor necrosis factor TNFα-induced E-Selectin expression and function in human umbilical vein endothelial cells (HUVEC). Exposure of HUVEC to 50 ng/ml TNFα resulted in increased leukocyte transmigration through the endothelial monolayer and E-Selectin expression, in association with augmented phosphorylation of both p66Shc on Ser36 and the stress kinase c-Jun NH2-terminal protein kinase (JNK)-1/2, and higher intracellular reactive oxygen species (ROS) levels. Overexpression of p66Shc in HUVEC resulted in enhanced p66Shc phosphorylation on Ser36, increased ROS and E-Selectin levels, and amplified endothelial cell permeability and leukocyte transmigration through the HUVEC monolayer. Conversely, overexpression of a phosphorylation-defective p66Shc protein, in which Ser36 was replaced by Ala, did not augment ROS and E-Selectin levels, nor modify cell permeability or leukocyte transmigration beyond those found in wild-type cells. Moreover, siRNA-mediated silencing of p66Shc resulted in marked reduction of E-Selectin expression and leukocyte transmigration. In conclusion, p66Shc acts as a novel intermediate in the TNFα pathway mediating endothelial dysfunction, and its action requires JNK-dependent phosphorylation of p66Shc on Ser36.

Context.—Learning the characteristics of frozen tissue samples stored in tumor banks for biological studies remains a problem. Objective.—To assess the use of touch imprint cytology on fresh tissue samples as a rapid and reliable method of determining the presence and quantity of neoplastic cells before freezing. Design.—Touch imprint cytology was performed on 259 specimens of operable breast cancer. Touch imprints were prepared from fresh tissue specimens before freezing samples for storage. Each tumor sample was imprinted on a glass slide and stained with hematoxylin-eosin. Tumor cellularity was quantified as negative, poor, moderate, or rich. Results.—A significant correlation was found between samples with a tumor size greater than 2 cm and high tumor cellularity (P = .03; χ2 test). Furthermore, 35% of ductal tumors showed higher tumor cellularity compared with lobular tumors (P < .001; χ2 test). No association was found between lymph node status and tumor grade. When samples for which more than 2 imprints were available were examined, tumor cellularity among imprints of the same sample showed an overall agreement of 0.67 (P < .001; κ statistic). It was also determined that the higher the cellularity, the higher the agreement. Our data also showed concordance of 0.87 (P < .001; κ statistic) between touch imprint cytology imprints and histologic sections from contiguous tumor. Moreover, 11 randomly selected samples underwent DNA extraction, polymerase chain reaction, and sequencing to verify the feasibility of DNA analyses. We found that DNA from touch imprint cytology was amplifiable and suitable for direct sequencing. Conclusions.—Touch imprint cytology may represent an important step in the quality control of tumor cellularity of breast cancer specimens designed to be stored in tumor biobanks and a valid method for assessing the suitability of such tissue for further biomorphologic and biomolecular applications.